Abstract

Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible to identify and trace individual transmission chains of viruses such as influenza virus during the course of an epidemic. Here we sequenced 153 pandemic influenza H1N1/09 virus genomes from United Kingdom isolates from the first (127 isolates) and second (26 isolates) waves of the 2009 pandemic and used their sequences, dates of isolation, and geographical locations to infer the genetic epidemiology of the epidemic in the United Kingdom. We demonstrate that the epidemic in the United Kingdom was composed of many cocirculating lineages, among which at least 13 were exclusively or predominantly United Kingdom clusters. The estimated divergence times of two of the clusters predate the detection of pandemic H1N1/09 virus in the United Kingdom, suggesting that the pandemic H1N1/09 virus was already circulating in the United Kingdom before the first clinical case. Crucially, three clusters contain isolates from the second wave of infections in the United Kingdom, two of which represent chains of transmission that appear to have persisted within the United Kingdom between the first and second waves. This demonstrates that whole-genome analysis can track in fine detail the behavior of individual influenza virus lineages during the course of a single epidemic or pandemic.

Simplified BEAST tree showing distribution of United Kingdom isolates in the context of global pandemic H1N1/09 virus isolates. United Kingdom lineages are shown with red lines, and all other lineages are shown with black lines. United Kingdom-specific clusters are indicated by gray boxes with adjacent cluster labels. Red dots indicate nodes with ≥95% posterior support, and orange dots indicate nodes with posterior support of <95% but ≥80%. Amino acid changes which characterize global cluster 7 are shown adjacent to the branches on which they likely occurred. Known (or suspected) importations are indicated with an asterisk adjacent to the terminal branch. Some groups with high posterior support are collapsed for clarity. Blue, pink, and yellow bars represent predetection, first-wave, and second-wave phases of the pandemic in the United Kingdom. The full tree with taxon names is shown in Fig. S1 in the supplemental material.

(A) Geographical distribution of viruses belonging to global clade-United Kingdom phylogenetic clusters. Two viruses isolated in the Republic of Ireland were also included. Magnified views of the Midlands (B) and the London area (C) are shown. Virus isolates are colored according to whether they were isolated in the first (pink) or second (blue) infection wave, with the United Kingdom cluster for each isolate identified by the cluster letter shown in Fig. 2.